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Biologics, Stem Cells, Growth Factors, Platelet-Rich Plasma, Hemarthrosis, and Scaffolds May Enhance ACL Surgical Treatment

Published:November 08, 2022DOI:https://doi.org/10.1016/j.arthro.2022.11.006

      Abstract

      Biologics including mesenchymal stem cells (MSCs), growth factors, and platelet-rich plasma (PRP) may enhance ACL reconstruction and even ACL primary repair. In addition, hemarthrosis after acute ACL injury represents a source of biologic factors. MSCs can differentiate into both fibroblasts and osteoblasts, potentially providing a transition between the ligament or graft and bone. MSCs also produce cytokines and growth factors necessary for cartilage, bone, ligament and tendon regeneration. MSC sources including bone marrow, synovium, adipose tissue, ACL-remnant, patellar tendon, and umbilical cord. Also, scaffolds may represent a tool for ACL tissue engineering. A scaffold should be porous allowing cell growth and flow of nutrients and waste, should be biocompatible, and might have mechanical properties matching the native ACL. Scaffolds have the potential to deliver bioactive molecules or stem cells. Synthetic and biologically derived scaffolds are widely available. ACL reconstruction improved outcome, ACL repair, and ACL tissue engineering are promising goals.
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      References:

        • Bollen S.
        Epidemiology of knee injuries: diagnosis and triage.
        British Journal of Sports Medicine. 2000; 34: 227
        • Grassi A.
        • Kim C.
        • Marcheggiani Muccioli G.M.
        • Zaffagnini S.
        • Amendola A.
        What Is the Mid-term Failure Rate of Revision ACL Reconstruction? A Systematic Review.
        Clin Orthop Relat Res. 2017; 475: 2484-2499
        • Uchida R.
        • Jacob G.
        • Shimomura K.
        • Horibe S.
        • Nakamura N.
        Biological Augmentation of ACL Repair and Reconstruction: Current Status and Future Perspective.
        Sports Med Arthrosc Rev. 2020; 28: 49-55
        • Hexter A.T.
        • Sanghani-Kerai A.
        • Heidari N.
        • et al.
        Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction.
        Knee Surg Sports Traumatol Arthrosc. 2021; 29: 3678-3688
        • DeHaven K.E.
        Diagnosis of acute knee injuries with hemarthrosis.
        Am J Sports Med. 1980; 8: 9-14
        • Leong N.L.
        • Petrigliano F.A.
        • McAllister D.R.
        Current tissue engineering strategies in anterior cruciate ligament reconstruction.
        J Biomed Mater Res A. 2014; 102: 1614-1624
        • Ouyang H.W.
        • Goh J.C.
        • Lee E.H.
        Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model.
        Am J Sports Med. 2004; 32: 321-327
        • Lim J.K.
        • Hui J.
        • Li L.
        • Thambyah A.
        • Goh J.
        • Lee E.H.
        Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction.
        Arthroscopy. 2004; 20: 899-910
        • Soon M.Y.
        • Hassan A.
        • Hui J.H.
        • Goh J.C.
        • Lee E.H.
        An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model: a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration.
        Am J Sports Med. 2007; 35: 962-971
        • Sun Y.
        • Chen W.
        • Hao Y.
        • et al.
        Stem Cell-Conditioned Medium Promotes Graft Remodeling of Midsubstance and Intratunnel Incorporation After Anterior Cruciate Ligament Reconstruction in a Rat Model.
        Am J Sports Med. 2019; 47: 2327-2337
        • Wang R.
        • Xu B.
        • Xu H.G.
        Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model.
        Cell Physiol Biochem. 2017; 41: 213-226
        • Wei X.
        • Mao Z.
        • Hou Y.
        • et al.
        Local administration of TGFβ-1/VEGF165 gene-transduced bone mesenchymal stem cells for Achilles allograft replacement of the anterior cruciate ligament in rabbits.
        Biochem Biophys Res Commun. 2011; 406: 204-210
        • Dong Y.
        • Zhang Q.
        • Li Y.
        • Jiang J.
        • Chen S.
        Enhancement of tendon-bone healing for anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells infected with BMP-2.
        Int J Mol Sci. 2012; 13: 13605-13620
        • Chen B.
        • Li B.
        • Qi Y.-J.
        • et al.
        Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.
        Scientific Reports. 2016; 625940
        • Wang Y.
        • Shimmin A.
        • Ghosh P.
        • et al.
        Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial.
        Arthritis Res Ther. 2017; 19: 180
        • Hevesi M.
        • LaPrade M.
        • Saris D.B.F.
        • Krych A.J.
        Stem Cell Treatment for Ligament Repair and Reconstruction.
        Curr Rev Musculoskelet Med. 2019; 12: 446-450
        • Centeno C.
        • Markle J.
        • Dodson E.
        • et al.
        Symptomatic anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow concentrate and platelet products: a non-controlled registry study.
        J Transl Med. 2018; 16: 246
        • Silva A.
        • Sampaio R.
        • Fernandes R.
        • Pinto E.
        Is there a role for adult non-cultivated bone marrow stem cells in ACL reconstruction?.
        Knee Surg Sports Traumatol Arthrosc. 2014; 22: 66-71
        • Sakaguchi Y.
        • Sekiya I.
        • Yagishita K.
        • Muneta T.
        Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source.
        Arthritis Rheum. 2005; 52: 2521-2529
        • Shirasawa S.
        • Sekiya I.
        • Sakaguchi Y.
        • Yagishita K.
        • Ichinose S.
        • Muneta T.
        In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells.
        J Cell Biochem. 2006; 97: 84-97
        • Ju Y.J.
        • Muneta T.
        • Yoshimura H.
        • Koga H.
        • Sekiya I.
        Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing.
        Cell Tissue Res. 2008; 332: 469-478
        • Matsumoto T.
        • Ingham S.M.
        • Mifune Y.
        • et al.
        Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells.
        Stem Cells Dev. 2012; 21: 859-872
        • Matsumoto T.
        • Sato Y.
        • Kobayashi T.
        • et al.
        Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction.
        Am J Sports Med. 2021; 49: 3508-3518
        • Zhang X.
        • Ma Y.
        • Fu X.
        • et al.
        Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.
        Sci Rep. 2016; 619073
        • Eagan M.J.
        • Zuk P.A.
        • Zhao K.W.
        • et al.
        The suitability of human adipose-derived stem cells for the engineering of ligament tissue.
        J Tissue Eng Regen Med. 2012; 6: 702-709
        • Alentorn-Geli E.
        • Seijas R.
        • Martínez-De la Torre A.
        • et al.
        Effects of autologous adipose-derived regenerative stem cells administered at the time of anterior cruciate ligament reconstruction on knee function and graft healing.
        Journal of Orthopaedic Surgery. 2019; 272309499019867580
        • Mifune Y.
        • Matsumoto T.
        • Ota S.
        • et al.
        Therapeutic potential of anterior cruciate ligament-derived stem cells for anterior cruciate ligament reconstruction.
        Cell Transplant. 2012; 21: 1651-1665
        • Mifune Y.
        • Matsumoto T.
        • Takayama K.
        • et al.
        Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction.
        Biomaterials. 2013; 34: 5476-5487
        • Zhang S.
        • Matsumoto T.
        • Uefuji A.
        • et al.
        Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential.
        BMC Musculoskelet Disord. 2015; 16: 390
        • Lui P.P.
        • Wong O.T.
        • Lee Y.W.
        Application of tendon-derived stem cell sheet for the promotion of graft healing in anterior cruciate ligament reconstruction.
        Am J Sports Med. 2014; 42: 681-689
        • Jang K.M.
        • Lim H.C.
        • Jung W.Y.
        • Moon S.W.
        • Wang J.H.
        Efficacy and Safety of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Anterior Cruciate Ligament Reconstruction of a Rabbit Model: New Strategy to Enhance Tendon Graft Healing.
        Arthroscopy. 2015; 31: 1530-1539
        • Moon S.W.
        • Park S.
        • Oh M.
        • Wang J.H.
        Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study.
        Knee Surgery & Related Research. 2021; 33: 32
        • Shao H.J.
        • Lee Y.T.
        • Chen C.S.
        • Wang J.H.
        • Young T.H.
        Modulation of gene expression and collagen production of anterior cruciate ligament cells through cell shape changes on polycaprolactone/chitosan blends.
        Biomaterials. 2010; 31: 4695-4705
        • Gurlek A.C.
        • Sevinc B.
        • Bayrak E.
        • Erisken C.
        Synthesis and characterization of polycaprolactone for anterior cruciate ligament regeneration.
        Mater Sci Eng C Mater Biol Appl. 2017; 71: 820-826
        • Han F.
        • Zhang P.
        • Chen T.
        • Lin C.
        • Wen X.
        • Zhao P.
        A LbL-Assembled Bioactive Coating Modified Nanofibrous Membrane for Rapid Tendon-Bone Healing in ACL Reconstruction.
        Int J Nanomedicine. 2019; 14: 9159-9172
        • Koh J.L.
        • Szomor Z.
        • Murrell G.A.
        • Warren R.F.
        Supplementation of rotator cuff repair with a bioresorbable scaffold.
        Am J Sports Med. 2002; 30: 410-413
        • Lu H.H.
        • Cooper Jr., J.A.
        • Manuel S.
        • et al.
        Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies.
        Biomaterials. 2005; 26: 4805-4816
        • Tang Y.
        • Tian J.
        • Li L.
        • et al.
        Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering.
        Tissue Eng Regen Med. 2021; 18: 819-830
        • Tanaka N.
        • Sakahashi H.
        • Hirose K.
        • Ishima T.
        • Ishii S.
        Augmented subscapularis muscle transposition for rotator cuff repair during shoulder arthroplasty in patients with rheumatoid arthritis.
        J Shoulder Elbow Surg. 2006; 15: 2-6
        • Li Y.
        • Guo X.
        • Dong S.
        • et al.
        A triple-coated ligament graft to facilitate ligament-bone healing by inhibiting fibrogenesis and promoting osteogenesis.
        Acta Biomater. 2020; 115: 160-175
        • Parry J.A.
        • Wagner E.R.
        • Kok P.L.
        • et al.
        A Combination of a Polycaprolactone Fumarate Scaffold with Polyethylene Terephthalate Sutures for Intra-Articular Ligament Regeneration.
        Tissue Eng Part A. 2018; 24: 245-253
        • Buma P.
        • Kok H.J.
        • Blankevoort L.
        • Kuijpers W.
        • Huiskes R.
        • Van Kampen A.
        Augmentation in anterior cruciate ligament reconstruction-a histological and biomechanical study on goats.
        Int Orthop. 2004; 28: 91-96
        • Badhe S.P.
        • Lawrence T.M.
        • Smith F.D.
        • Lunn P.G.
        An assessment of porcine dermal xenograft as an augmentation graft in the treatment of extensive rotator cuff tears.
        J Shoulder Elbow Surg. 2008; 17: 35s-39s
        • Song L.
        • Olsen R.E.
        • Spalazzi J.P.
        • Davisson T.
        Biomechanical evaluation of acellular collagen matrix augmented Achilles tendon repair in sheep.
        J Foot Ankle Surg. 2010; 49: 438-441
        • Murray M.M.
        • Spindler K.P.
        • Abreu E.
        • et al.
        Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament.
        J Orthop Res. 2007; 25: 81-91
        • Altman G.H.
        • Horan R.L.
        • Lu H.H.
        • et al.
        Silk matrix for tissue engineered anterior cruciate ligaments.
        Biomaterials. 2002; 23: 4131-4141
        • Barber F.A.
        • McGarry J.E.
        • Herbert M.A.
        • Anderson R.B.
        A biomechanical study of Achilles tendon repair augmentation using GraftJacket matrix.
        Foot Ankle Int. 2008; 29: 329-333
        • Bond J.L.
        • Dopirak R.M.
        • Higgins J.
        • Burns J.
        • Snyder S.J.
        Arthroscopic replacement of massive, irreparable rotator cuff tears using a GraftJacket allograft: technique and preliminary results.
        Arthroscopy. 2008; 24 (e401): 403-409
        • Murray M.M.
        • Flutie B.M.
        • Kalish L.A.
        • et al.
        The Bridge-Enhanced Anterior Cruciate Ligament Repair (BEAR) Procedure: An Early Feasibility Cohort Study.
        Orthop J Sports Med. 2016; 42325967116672176
        • Murray M.M.
        • Kalish L.A.
        • Fleming B.C.
        • et al.
        Bridge-Enhanced Anterior Cruciate Ligament Repair: Two-Year Results of a First-in-Human Study.
        Orthop J Sports Med. 2019; 72325967118824356
        • Park S.H.
        • Choi Y.J.
        • Moon S.W.
        • et al.
        Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.
        Arthroscopy. 2018; 34: 166-179
        • Liu A.
        • Xue G-h
        • Sun M.
        • et al.
        3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction.
        Scientific Reports. 2016; 621704
        • Ge Z.
        • Goh J.C.
        • Lee E.H.
        The effects of bone marrow-derived mesenchymal stem cells and fascia wrap application to anterior cruciate ligament tissue engineering.
        Cell Transplant. 2005; 14: 763-773
        • Fan H.
        • Liu H.
        • Toh S.L.
        • Goh J.C.H.
        Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model.
        Biomaterials. 2009; 30: 4967-4977
        • Fan H.
        • Liu H.
        • Wong E.J.
        • Toh S.L.
        • Goh J.C.
        In vivo study of anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold.
        Biomaterials. 2008; 29: 3324-3337
        • Teuschl A.
        • Heimel P.
        • Nürnberger S.
        • van Griensven M.
        • Redl H.
        • Nau T.
        A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep.
        Am J Sports Med. 2016; 44: 1547-1557
        • Figueroa D.
        • Espinosa M.
        • Calvo R.
        • et al.
        Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model.
        Knee Surg Sports Traumatol Arthrosc. 2014; 22: 1196-1202
        • Proffen B.L.
        • Vavken P.
        • Haslauer C.M.
        • et al.
        Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model.
        Am J Sports Med. 2015; 43: 320-330
        • Jacobs C.A.
        • Hunt E.R.
        • Conley C.E.
        • et al.
        Dysregulated Inflammatory Response Related to Cartilage Degradation after ACL Injury.
        Med Sci Sports Exerc. 2020; 52: 535-541
        • Kingery M.T.
        • Anil U.
        • Berlinberg E.J.
        • Clair A.J.
        • Kenny L.
        • Strauss E.J.
        Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction.
        The American Journal of Sports Medicine. 2022; 50: 451-460
        • Knuth C.A.
        • Clark M.E.
        • Meeson A.P.
        • et al.
        Low oxygen tension is critical for the culture of human mesenchymal stem cells with strong osteogenic potential from haemarthrosis fluid.
        Stem Cell Rev Rep. 2013; 9: 599-608
        • Lee S.Y.
        • Miwa M.
        • Sakai Y.
        • et al.
        In vitro multipotentiality and characterization of human unfractured traumatic hemarthrosis-derived progenitor cells: A potential cell source for tissue repair.
        J Cell Physiol. 2007; 210: 561-566
        • Lee S.Y.
        • Miwa M.
        • Sakai Y.
        • Kuroda R.
        • Niikura T.
        • Kurosaka M.
        Osteogenic potential of cells in vitro derived from haemarthrosis of the knee induced by injury to the anterior cruciate ligament.
        J Bone Joint Surg Br. 2006; 88: 129-133
        • Anz A.W.
        • Branch E.A.
        • Rodriguez J.
        • et al.
        Viable Stem Cells Are in the Injury Effusion Fluid and Arthroscopic Byproducts From Knee Cruciate Ligament Surgery: An In Vivo Analysis.
        Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2017; 33: 790-797